Alkylidene branched lupane derivatives: Synthesis and antitumor activity

Several novel alkylidene branched lupane derivatives have been prepared. Many of these compounds showed a significant cytotoxicity. The most active compound, 2-methylene-betulonic acid, showed IC50 values between 0.2 and 0.6 μM for 15 different human cancer cell lines. Cytotoxicity can be improved by encapsulation in liposomes. These compounds act by triggering apoptotic cell death as shown by DNA-laddering experiments and acridine orange/ethidium bromide staining.

Graphical AbstractSeveral novel alkylidene branched lupane derivatives have been prepared and tested for cytotoxicity. They act by triggering apoptosis as shown by DNA-laddering experiments and acridine orange/ethidium bromide staining.Figure optionsDownload as PowerPoint slideHighlights
► In this study we synthesize betulonate derivatives.
► The compounds were tested for their antitumor activity using 15 different human cancer cell lines.
► The derivatives show a significant higher activity than parent betulonic acid when attaching a methylene group to ring A.
► The compounds act by apoptosis.